TMEM38A

TRIC-A is a 33kDa^[7] transmembrane protein, expressed predominantly in excitable tissues including skeletal muscle and brain.^[5] Its N-terminal region is located in the SR lumen^[7] or within the nucleus while its C-terminal region projects into the cytoplasm.^[5] In situ, TRIC-A forms homo-trimers, producing its "bullet-shaped" three-dimensional structure (see Venturi et al. (2012), Figure 1 for a three-dimensional rendering of TRIC-A).

TRIC-A is permeable to both Na⁺ and K⁺ but not divalent cations like Ca²⁺.^[5] The channel exhibits marked voltage-dependence, becoming more open when the cytosol is more positively charged than the ER lumen. TMEM38A-knockout mice exhibit reduced Ryanodine receptor 1-mediated Ca²⁺ release;^[5] as such, K⁺ flux into the SR through TRIC-A is thought to support RyR1-mediated efflux of Ca²⁺ ions from the sarcoplasmic reticulum into the cytosol. These knockouts also develop hypertension during early adulthood, whereas transgenic mice overexpressing TRIC-A develop hypotension. These results are thought to reflect a role for TRIC-A in the excitability of vascular smooth muscle cells.